tbuckley/cabot-search huggingface dataset:
Molecular parameters impacting the success rate of a lung cancer PDX model.
Authors: Ziyi Li, Shawna Marie Hubert, Ran Zhang, Xingzhi Song, Tatiana Karpinets, Annikka Weissferdt, Latasha Little, Mohammad Mohammad, Curtis Gumbs, Marcelo Vailati Negrao, Jianhua Zhang, Apar Pataer, Stephen Swisher, Ara A. Vaporciyan, Jack A. Roth, John Heymach, Boris Sepesi, Don Lynn Gibbons, Bingliang Fang, Jianjun Zhang
Journal: Journal of Clinical Oncology (2022)

e20592 Background: Patient-derived xenograft (PDX) models can provide renewable cancer tissue resources, are being increasingly utilized for the molecular characterizations of cancers and preclinical studies on drug activities, and have the potential to advance biomarker identification. Previous research has demonstrated that PDX tumors preserve the histologic and morphologic characteristics and gene expression and mutation patterns of primary tumors, and correlate to patient survival. Tumor histological subtypes and differentiation grades are known to contribute to the success of PDX intake, but little is known about how molecular features associate with the success of PDX engraftment or whether PDX preserves subclonal architecture of primary tumors. Methods: To fill this void, we analyzed 252 primary tumor samples from the SPORE/ICON project at MD Anderson Cancer Center that were used for generating PDXs and had comprehensive genomic, transcriptomic, and immune profiling data available to evaluate the parameters impacting the intake success of lung cancer PDXs. In order to establish the impact of molecular features on PDX intake success we also assessed the fidelity of PDX in representing the molecular features of this cohort of primary tumors. Results: Only 36% of the primary tumors in this study successfully generated a PDX, with Squamous Cell Carcinoma PDX demonstrating an intake rate of 67% and Adenocarcinoma PDX demonstrating an intake rate of 21%. Genomic architecture derived from whole exome sequencing showed not only 43% (38-48%) of mutations shared, but also similar clonal architecture between primary tumors and PDX. Higher copy number aberration burden, high tumor purity and low immune infiltration in primary tumors were found to be associated with successful intake of PDX. Transcriptomics revealed 6,103 genes differentially expressed between primary tumors with successful PDX intake versus those which were unsuccessful. Pathway analysis of these genes indicated that inhibition of cell proliferation, signaling, and migration as well as DNA replication, recombination and repair were associated with PDX intake failure regardless of histology. Conclusions: These findings indicate that PDX intake success is regulated by molecular features and multiomic evaluation of lung cancer primary tumors can be used as a marker for determining which samples to use for PDX model generation.
Delayed head and neck cancer detection and treatment by patient-insurance and community-level socioeconomic status.
Authors: Jason Semprini
Journal: Journal of Clinical Oncology (2022)

e18600 Background: Health insurance helps Head and Neck Cancer (HNC) patients overcome delays for accessing treatment. To overcome gaps in access, policymakers have expanded insurance coverage. If, however, access to timely treatment still varies by insurance status, disparities may persist. Methods: I analyzed data from the Surveillance Epidemiology and End Results program’s “Specialized HNC-HPV” datafile (2010-2016), which categorizes each HNC case into a socioeconomic status (SES) quintile based on the patient’s census-tract of residence. Patients were grouped by having private insurance, Medicare, Medicaid, or being uninsured. Two binary outcome variables were analyzed for differences by insurance status across SES quintiles: a distant stage diagnosis and initiating treatment at least two months after diagnosis. To account for the dynamic nature of HNC, the sample was stratified by Human Papilloma Virus (HPV)-association. Using a linear probability regression model, I tested for differences between insurance categories within each SES quintile. Results: Across all SES quintiles, HPV-negative cancer patients insured by Medicaid had higher rates of distant stage diagnoses and delayed treatment than privately insured patients. Uninsured patients also had higher rates of delayed detection and treatment initiation than privately insured patients. There were no significant differences in the rate of distant-stage diagnoses between privately insured and Medicare patients. However, for all SES quintiles, patients insured by Medicare had higher rates of delayed treatment than privately insured patients. Results were consistent for HPV-positive HNCs, but differences were not significant across all SES quintiles. Conclusions: Even after conditioning on community-level SES, a HNC patient’s insurance type may be associated with delayed detection and treatment. While expanding insurance remains a priority, policymakers must also improve the quality of public health insurance programs to ensure equitable access to timely HNC care.[Table: see text]
The potential use of blood-based tumor fibrosis markers as diagnostic and prognostic biomarkers in patients with biliary tract cancer.
Authors: Troels Dreier Christensen, Christina Jensen, Nicholas Willumsen, Ole Larsen, Bonna Leerhøy, Carsten Palnaes Hansen, Kasper Madsen, Dorte Nielsen, Julia S. Johansen
Journal: Journal of Clinical Oncology (2022)

4082 Background: Patients with biliary tract cancer (BTC) have a very poor prognosis. A better understanding of the disease and potential novel biomarkers are needed. BTC is characterized by a collagen-rich desmoplastic extracellular matrix (ECM), and tumor fibrosis is linked to cancer progression and treatment resistance. We tested the diagnostic and prognostic use of seven circulating biomarkers associated with ECM remodeling. We evaluated both pro-peptides (pro-peptide of collagen type III (Pro-C3), VI (PRO-C6), XI (PRO-C11)) and degradation fragments (matrix metalloproteinase (MMP) degraded collagen type III (C3M) and IV (C4M), granzyme B degraded collagen type IV (C4G), citrullinated and MMP degraded vimentin fragment (VICM)). Methods: The study included 269 patients with all stages of BTC (intrahepatic cholangiocarcinoma (CC) (n=124), extrahepatic CC (n=89), and gall bladder cancer (n=56)), and 49 patients with benign biliary tract disease. Serum samples were collected from the patients with BTC before surgery (n=36), 1 st line (n=199), and 2 nd line (n=56) treatment. A total of 22 patients had samples collected at two timepoints. The seven ECM markers and carbohydrate antigen 19-9 (CA19-9) were analyzed using enzyme-linked immunosorbent assay (ELISA) and electrochemiluminescence immunoassay. Results: The levels of C3M, C4M, PRO-C3, PRO-C6, PRO-C11, and VICM were significantly elevated in patients with BTC compared to patients with benign disease (Wilcoxon test, adjusted p-value &lt; 0.05). Area under receiver operating characteristics curve (AUC) identified PRO-C3 (AUC=0.87) as the ECM marker that best discriminated between patients with BTC and controls. A model combining PRO-C3 and CA19-9 further improved the diagnostic accuracy (AUC=0.97). Elevated levels of four markers (C3M, C4M, PRO-C3 and PRO-C6) before 1 st line treatment for BTC were associated with short overall survival (OS) in separate multivariate cox regression analyses adjusting for CA19-9, performance status, and stage. Similarly, elevated levels of PRO-C3 and PRO-C6 before 2 nd line treatment were associated with short OS (Table). Conclusions: We identified specific blood-based collagen fragments as potential novel biomarkers for BTC. Our results indicate that patients with BTC have an elevated collagen remodeling, and that increased collagen turnover is associated with a poor prognosis for these patients. [Table: see text]
Proposing a social determinants of health (SDOH) EMR dashboard to improve heath equity in cancer care.
Authors: Luis E. Raez, Monica E Puga, Terri Thompson, Meredith Feinberg,, Vedner Guerrier, Kelly King, Brian Hunis, Kimberly Blandon
Journal: Journal of Clinical Oncology (2022)

e18548 Background: There are biological differences in the clinical outcomes of Black or Hispanic cancer patients compared with non-Hispanic Whites (NHWs); however minorities have disadvantages in social determinants of health (SDOH) that influence cancer outcomes too. The World Health Organization defines SODH as the conditions in which people are born, grow, live, work, age, and maintains that they are largely responsible for health inequities . Most the oncology professionals do not consider that this issue is necessarily part of their scope of practice and they rely on social workers and others to address these issues, and they are not aware that SDOH can impact clinical outcomes of cancer patients. Methods: Memorial Cancer Institute (MCI) part of the Memorial Healthcare System (MHS) is the 3 rd largest Public Health Care System in the country. We found important disparities in immunotherapy outcomes in our MCI minority lung cancer patients ( Raez LE. Research Trends. 2021 Feb (20) 63–74 and Dickson F. JTO Vol. 16 (10) S904–5), some of these are related to SDOH. In order to increase awareness of SDOH and identify the impact of SDOH on cancer outcomes, our MHS value-based care team has been working to incorporate SDOH screening and follow-up as an important part of treatment plan development since 2018. At that time, MHS implemented an SDOH dashboard in our EPIC EMR to show the SDOH areas of risk. In 2021, MHS built a best practice alert in Epic to notify health care providers about SDOH issues that might impact treatment outcomes. Results: MHS has implemented a SDOH dashboard in the EPIC EMR that is accessible and easily noticed by the providers and updated constantly by our social workers and other health professionals screening for SDOH. Providers do not need to do extra work other than to be aware that the best cancer treatment that they are recommending for a patient might not have the desired outcome if some of these 13 SDOH are not considered during the planning phase of treatment. The SDOH dashboard uses color coding to indicate if any SDOH is at risk (red) or not at risk or low risk (green) allowing the provider to easily focus in on areas of concern when SDOH is reviewed. Conclusions: Using an easy to access and easy to read SDOH dashboard in the EMR allows oncology providers to address SDOH in the development of oncology treatment plans which we believe will lead to improved health care outcomes.[Table: see text]
Mammography screening is associated with more favorable breast cancer tumor characteristics and better overall survival: Case-only analysis of 3,739 Asian breast cancer patients.
Authors: Mikael Hartman, Zi Lin Lim, Peh Joo Ho, Alexis Jiaying Khng, Yen Shing Yeoh, Amanda Tse Woon Ong, Benita Kiat Tee Tan, Ern Yu Tan, Su-Ming Tan, Geok Hoon Lim, Kiak Mien Veronique Tan, Jingmei Li
Journal: Journal of Clinical Oncology (2022)

e22500 Background: Early detection of breast cancer (BC) through mammography screening (MAM) is known to reduce mortality. We examined the differential effect that mammography has on BC characteristics and overall survival and the sociodemographic determinants of MAM utilisation in a multi-ethnic Asian population. Methods: This study included 3,739 BC patients from the Singapore Breast Cancer Cohort (2010–2018). Self-reported socio-demographic characteristics were collected using a structured questionnaire. Clinical data were obtained through medical records. Patients were classified as screeners (last screening mammogram ≤two years before diagnosis), non-screeners (aware but did not attend or last screen &gt; 2years) and those unaware of MAM. Associations between MAM behaviour (MB) and sociodemographic factors and MB and tumour characteristics were examined using multinomial regression. Ten-year overall survival was modelled using Cox regression. Results: Patients unaware of screening were more likely diagnosed with late stage (OR stage III vs stage I(Ref) [95%CI]:4.94[3.45-7.07], p &lt; 0.001), high grade (OR poorly- vs well-differentiated(reference) : 1.53 [1.06-2.20], p = 0.022), nodal-positive, large size (OR &gt; 5cm vs ≤2cm(reference) : 5.06 [3.10-8.25], p &lt; 0.001), and HER2-positive tumors (OR HER2-negative VS -positive(reference) : 0.72[0.53-0.97], p = 0.028). Similar trends were observed between screeners and non-screeners with smaller effect sizes. Overall survival was significantly shorter than screeners in the both groups(non-screeners HR: 1.89 [1.22-2.94], p = 0.005; unaware HR: 2.90[1.69-4.98], p &lt; 0.001). Non-screeners and those unaware were less health-conscious, older, of Malay ethnicity, less highly educated, of lower socioeconomic status, more frequently ever smokers and less physically active. Among screeners, there were more reported personal histories of benign breast surgeries or gynaecological conditions and positive family history of breast cancer. Conclusions: Mammography attendance is associated with more favourable BC characteristics and overall survival. Disparities in the utility of MAM services suggest that different strategies may be needed to improve MAM uptake.
Anti-HER2 antibody inetetamab plus camrelizumab and utidelone for pretreated HER2-positive advanced breast cancer: A single-arm, multicenter, phase 2 study.
Authors: Min Yan, Huimin Lv, Limin Niu, Mengwei Zhang, Huiai Zeng, Shengnan Zhao, Jing Wang, Huihui Sun, Shumin Chen
Journal: Journal of Clinical Oncology (2022)

e13030 Background: Treatment options for patients with HER2-positive breast cancer after progression on two or more lines of HER2-directed therapies are scarce. Inetetamab, a novel anti-HER2 antibody, exhibits the same binding affinity to HER2 antigen and antibody-dependent cell-mediated cytotoxicity as trastuzumab. Previous studies have demonstrated the treatment potential of PD-1 inhibitor combined with HER2-targeted therapy in HER2-positive gastric or gastroesophageal junction cancer. Utidelone, a genetically engineered epothilone analogue, has shown promising efficacy in heavily pretreated metastatic breast cancer. This study aimed to investigated inetetamab plus camrelizumab (anti-PD-1 antibody) and utidelone in patients with HER2-positive recurrent or metastatic breast cancer who had progressed after at least two lines of HER2-directed therapies with trastuzumab and tyrosine kinase inhibitors (TKIs). Methods: In this phase 2 study (NCT04681287), patients received intravenous camrelizumab (200 mg once every 3 weeks), inetetamab (8 mg/kg loading dose then 6 mg/kg, day 1), and utidelone (30 mg/m 2 , days 1-5) until disease progression or intolerable toxicity. The primary endpoint was 3-month progression-free survival (PFS) rate according to the Response Evaluation Criteria In Solid Tumors, version 1.1. Secondary endpoints included objective response rate (ORR), PFS, overall survival, and safety. Simon’s two-stage design was adopted for this study. Results: Between April 2021 and January 2022, a total of 27 patients were enrolled. As of January 2022, 20 patients could be analyzed. The median number of previous systemic therapies for advanced disease was three. Previous HER2-targeted therapies included trastuzumab (20 [100%]), pyrotinib (17 [85%]), lapatinib (7 [35%]), pertuzumab (3 [15%]), and margetuximab (2 [10%]). The first stage required 10 patients, and 8 of them were free from progression at 3 months. The study proceeded to the second stage for another 31 patients, and the accrual is ongoing. The 3-month PFS rate in 20 patients was 75%. The ORR was 30% (6/20); one (5%) patient achieved complete response. The most common treatment-related adverse events (TRAEs) were peripheral neuropathy (19 [98%]), capillary proliferation (19 [98%]), alopecia (18 [90%]), and fatigue (7 [35%]). Grade ≥3 TRAEs included peripheral neuropathy (2 [10%]) and rash (1 [5%]). No treatment-related treatment discontinuation or deaths occurred. Conclusions: Inetetamab plus camrelizumab and utidelone showed promising efficacy and acceptable safety profile in patients with HER2-positive advanced breast cancer after progression on at least two lines of HER2-directed therapies with trastuzumab and TKIs. Clinical trial information: NCT04681287.
VOYAGER (KSCC1902): A single-arm, multicenter, phase II study of early induction of nivolumab during second-line treatment with taxane ± ramucirumab for advanced gastric or gastro-esophageal junction cancer.
Authors: Hiroo Katsuya, Akitaka Makiyama, Tomomi Kashiwada, Yudai Shinohara, Qingjiang Hu, Satoshi Otsu, Akira Yoneda, Yasunori Emi, Nobuya Ishibashi, Eto Kojiro, Masato Nakamura, Mototsugu Shimokawa, Eiji Oki, Hiroshi Saeki, Masaki Mori
Journal: Journal of Clinical Oncology (2022)

4028 Background: Although nivolumab prolonged overall survival in 3rd or later line treatment for advanced gastric cancer in the ATTRACTION-2 study, only a small number of patients respond or achieve stable disease. Previous reports have shown that low tumor burden at the start of treatment was potentially associated with efficacy to immunotherapy in some types of tumors, but it has not been studied in advanced gastric cancer. We conducted a clinical trial to evaluate the early induction of nivolumab. Methods: Eligible patients were unresectable advanced or recurrent gastric or gastro-esophageal junction cancer, histologically confirmed to be adenocarcinoma regardless of PD-L1 expression. Patients who were refractory to or intolerant of fluoropyrimidines had a complete or partial response after at least three cycles of taxane ± ramucirumab, and were confirmed to be either of the following conditions; disease progression by imaging tests, an increase of tumor markers, exacerbation of symptoms, and intolerant of pretreatment. Patients received 240mg/body nivolumab every 2 weeks. The primary endpoint was the rate of progression-free survival (PFS) at 6 months (M), and the secondary endpoints included safety, overall survival (OS), response rate (RR), time to treatment failure (TTF), and duration of response (DOR). Based on assuming a threshold PFS at 6M of 16% and an expected PFS of 30% with the early induction of nivolumab, 39 patients were required for a power of 0.8 with a one-sided α of 0.1. Results: Between September 2019 and February 2021, 42 patients were enrolled in this study. The characteristics of patients were male/female: 28/14, median age: 71 years (range: 39-87), and performance status 0/1/2: 21/19/2. The PFS at 6M was 35.7% (80% confidence interval 26.4-45.1%), which means this trial met the primary endpoint. The median PFS and OS were 4.0M (95%CI:2.3–5.7) and 10.9M (95%CI:9.9–16.0), respectively. Of 34 patients with baseline target legions, RR was 17.5% (all confirmed partial response) and the rate of stable disease was 41.2%. TTF, and DOR were 3.6M (95%CI:2.2–5.1), and 14.3M (95%CI:3.9–14.3), respectively. No new safety signals were observed. Conclusions: This study demonstrated an improvement of PFS at 6M in patients with advanced gastric cancer and might justify the strategy of early induction of nivolumab. Clinical trial information: jRCTs071190025.
The predictive and prognostic value of weight loss and body composition prior to and during treatment with immune checkpoint inhibitors in patients with recurrent or metastatic head and neck cancer.
Authors: Anna C. H. Willemsen, Nina De Moor, Jeroen Van Dessel, Michel Bila, Laura W.J. Baijens, Esther Hauben, Mari Van Den Hout, Ann Hoeben, Paul M. Clement, Annemie M.W.J. Schols
Journal: Journal of Clinical Oncology (2022)

e18027 Background: Response rates of immune checkpoint inhibitor (ICI) therapy for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) are relatively low. This study evaluates the predictive and prognostic value of weight loss and changes in body composition prior to and during ICI therapy in R/M HNSCC. Methods: This retrospective multicenter cohort study enrolled ninety-eight patients. Patient, tumor and treatment characteristics were retrieved from health records, including neutrophil and platelet-lymphocyte-ratio (NLR and PLR). Cachexia was defined according to the international consensus (Fearon et al. 2011). Skeletal muscle (SM), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) were evaluated on baseline and follow-up computed tomography scans at the third lumbar vertebrae level. Univariable and multivariable regression analysis were performed for six months progression free survival (PFS6m) and overall survival (OS). Results: Thirty-four patients (35%) experienced significant early weight loss (&gt; 2%) during the first six weeks of therapy. This subgroup presented a significantly higher NLR and PLR at baseline. NLR and PLR were significantly correlated with VAT and SAT index. Independent predictors of PFS6m were lower world health organization performance status (WHO PS) (HR 0.16 [95% CI 0.04-0.54] p = 0.003), higher baseline SAT index (HR 1.045 [95% CI 1.02-1.08] p = 0.003), and early weight loss &lt; 2% (HR 0.85 [95% CI 0.74-0.98] p = 0.03). WHO PS and baseline cachexia in combination with &gt; 2% early weight loss were independent predictors of OS (HR 2.09 [95% CI 1.11-3.92] p = 0.02, HR 2.18 [95% CI 1.13-4.21] p = 0.02). Conclusions: The combination of cachexia at baseline and weight loss during the first six weeks of ICI therapy is associated with worse OS in HNSCC patients treated with ICI therapy. Patients with early weight loss during ICI treatment show an increase in systemic inflammation. The mechanism of how adipose tissue interferes with ICI response needs further investigation.